Method and device for measurement of electrical bioimpedance

ABSTRACT

A method of measuring of an electrical bio-impedance, the method being characterized in that a symmetrical bipolar pulse-form periodical excitation signal (electrical current or voltage) is applied to the input ( 11 ) of the bio-object ( 1 ), a corresponding reaction of the bio-object to the mentioned excitation signal is measured from the output ( 12 ), which is connected to the input ( 201 ) of the synchronous detector ( 200 ). A symmetrical bipolar pulse-form periodical signal is also applied to the reference input ( 202 ) of the synchronous detector ( 200 ), whereby both pulse-form signals are shortened by the predetermined time interval in each half period of the signal, said time intervals being different for the excitation and reference signals. The proposed method ensures an increased accuracy of the impedance analysis by decreasing the influence of the higher harmonics in the spectra of the excitation and reference signals of the synchronous detectors to the measurement result. The use of the rectangular signals ensures that the device for implementing of the proposed method has a simple design and low power consumption.

TECHNICAL FIELD

The invention is related to the measurement of electrical impedance,particularly to measurement of the electrical bio-impedance, and isbased on the synchronous signal conversion or lock-in techniques usedfor converting of measuring signals for forming the measuring(excitation) signal as well as for demodulating the response signal fromthe object.

The main field of application of the invention is related to themeasurement of impedance in portable and/or implantable medical meansand apparatuses, which are used with the aim to get diagnostic resultsand to determine the conditions of implanted and/or implantable andtransplantable organs and tissues. The invention is directly aimed to beused in implantable medical devices, such as rate-adaptive cardiacpacemakers and monitors, and in monitors of transplantable andtransplanted organs.

RELATED PRIOR ART

The PCT application WO 01/19426 “Implantable Device and Method forLong-Term Detection and Monitoring of Congestive Heart Failure” has beendescribed a measuring device, which is mounted into the pacemaker, andobserves over the complications appearing in the cardiac blood vesselsystem and in the blood circulation in lungs. The method is based ondirecting various types of current/voltage excitation signals(rectangular waveform signal, sine wave signal, pulse signal, signalwith varying frequency) through the bio-object and measuring the inphaseand quadrature components of the electrical response to the excitation.The device measures the variations in the impedance of the cardiac bloodvessel system and of the blood circulation in lungs via measuring thecurrent flow through the object, the voltage drop forming on it and thephase shift between the excitation and response signals.

In the inventions WO 00/57953 and WO 00/57954 “A Rate Adaptivepacemaker” the device for bio-impedance measurement is used forobtaining information for adaptive control of cardiac pacing rate takinginto account the energetic balance of the myocardium.

U.S. Pat. No. 5,759,159 “Method and Apparatus for Apical Detection withComplex Impedance Measurement” (Jun. 2, 1998) describes thebio-impedance measurement device used for finding the apex of a dentalchannel. The apex can be found by measuring the amplitude and phasecharacteristics of the bio-impedance between the probe and biologicaltissue. The method is based on measuring the amplitude and phaserelationships of an electrical impedance in response to amulti-frequency excitation using a digital fast Fourier transformation(FFT).

The above described devices are not suitable for implantation becausetheir electronic circuitry is too complicated and energy consuming.

Nowadays low voltage and low power CMOS microelectronics technology issuitable for application in switching mode analogue and digital mixedsignal circuits. The extremely low power consumption is cruciallyimportant for the implantable devices operating during several yearswith the same battery.

Unfortunately, application of the switching mode electronics operatingwith pulse signals results in misleading measurement errors andmeasurement uncertainties due to the higher harmonics present in thepulse signals. Theoretically, application of pure sine wave signalswithout any higher harmonics is presumed for determination of thecomplex impedance. Therefore, application of the simplest rectangularwaveform pulses being the most suitable for use in CMOS electronics,introduces serious measurement errors [M. Min. and T. Parve,“Improvement of the vector analyser based on two-phase switching modesynchronous detection”, Measurement, Vol. 19 (1996), No. 2, pp.103-111].

To overcome the problem, usually the band-pass filters are introduced inorder to filter out the fundamental and to suppress the higherharmonics. This solution helps to solve the higher harmonics problemonly partly, because the highly selective band-pass filters have veryunstable phase characteristics. The exact tuning of such filters is alsorather complicated.

U.S. Pat. No. 5,063,937, A61B 5/05, “Multiple frequency bio-impedancemeasurement system”, B. N. Ezenwa, W. P. Couch, Nov. 12, 1991, describesthe closest prior art. In this document there is described a solutionfor a device for noninvasive measurement of the bio-impedance of aliving tissue, according to which the component of interest of theexcitation response of the bio-impedance (its active or reactive part)is demodulated by a synchronous detector, the reference signal of whichis a rectangular wave signal being in phase or in quadrature with theexcitation signal.

The systems operation is based on the switch-mode generator generatingrectangular pulses, but prior to being applied to the test objects inputthe excitation pulses pass the highly selective band-pass filter. Theband-pass filter is tuned to the main frequency of the excitationsignal, and therefore the filter suppresses the higher harmonics of theoriginal rectangular pulses, reducing in such a way the content ofhigher harmonics in the signals to be detected by the synchronousdetector and decreasing measurement errors, which are caused by higherharmonics.

The described above solution has the following main drawbacks.

Tuning of a highly selective band-bass filter to the fundamentalfrequency is a troublesome procedure with an instable result. The phaseshift between input and output can be compensated using sophisticatedelectronic circuits, which makes the excitation generator excessivelycomplicated and bulky.

Some problems arise also in connection with generating of the referencesignals used for driving the synchronous detector. In practice therectangular reference pulse signals have to be formed anew from thefiltered out pure sine wave excitation signal in order to eliminate thephase errors caused by the highly selective filter. Thus, someadditional electronic circuits are needed, but the complexity of acircuitry is extremely undesirable in implantable medical devices inconnection with which the compactness and low current consumption isrequired.

In addition, the described solution is not suitable for implementing inmodern CMOS technology because several electronic blocks operate in nearto linear mode.

SUMMARY OF THE INVENTION

The purpose of the invention is to increase the accuracy of measurementsof the electrical impedance and/or immittance, using the switch-modegeneration and demodulation of signals in the case of both analogue anddigital signal processing, retaining at the same time the characteristicsimplicity of the measurement method, as well as the simplicity and lowenergy consumption of the measuring device. The undesirable effectscaused by both the higher odd harmonics contained in the rectangularwave signals and by the sensitivity of traditional synchronous detectorsto odd higher harmonics are essentially suppressed or eliminated.

In traditional applications of synchronous detectors the strongestimpact to the demodulated signal is caused by the closest to the mainfrequency odd higher harmonics within the first decade, i.e. the 3rd,5th, 7th, and 9th harmonics, having typically the highest levels aswell. For example, the measurement error caused only by the 3rd harmonicof the rectangular signal having the level of ⅓ of the fundamental, cancause a relative measurement error of 1/9 or 11 percent. The resultingmeasurement error from all higher harmonics of the rectangular waveformcan extend up to 24 percent.

In addition to the amplitude errors also the phase errors appear fromapplication of the non sine wave signals. Though the phase errors remainrelatively smaller than the amplitude errors, their role can besignificant anyway, because the absolute value of the phase shift as arule does not exceed 45 degrees at the bio-impedance measurements.Therefore, the phase error of only some degrees results in a relativeerror in the range of 10 percent.

The essence of the measurement method according to the invention lies inreducing of the harmonics content of periodic and symmetrically bipolarpulse wave signals through shortening the duration of their constantvalue sections by a predetermined time intervals, during which thesignals can have different values, including the zero value (FIG. 2A).The zero value signal intervals present the simplest case of the method.The zero value means an absence of the signals physically and denote astepwise transition of the signal from one discrete value to another.These signal transitions can be, but must not be stepwise in principle.For example, the transitions can have different stepwise forms, orcompletely or piecewise linear forms as well. Only the shortening of theconstant value sections of the signals by the predetermined timeintervals has the principal significance.

The zero value intervals in FIG. 2A are determined so that the spectrumof the excitation signal will not contain the 3rd harmonic and thespectrum of the reference signal driving the synchronous detector willnot contain the 5th harmonic. In the respective mathematical expressionfor the spectrum of the shortened rectangular wave signal$\begin{matrix}{{f(x)} = {\frac{4a}{\pi}\lbrack {{\frac{\cos\quad b}{1}\sin\quad x} + {\frac{\cos\quad 3b}{3}\sin\quad 3x} + {\frac{\cos\quad 5b}{5}\sin\quad 5x} + \ldots} \rbrack}} \\{{= {\frac{4a}{\pi}{\sum\limits_{n = 0}^{\infty}{\frac{\cos\quad( {{2n} + 1} )b}{{2n} + 1} \times \sin\quad( {{2n} + 1} )x}}}},}\end{matrix}\quad$where:

a is the constant amplitude value of the pulse signal, and

b characterises the relative shortening of pulses and is equal to thelength of the signal's zero value interval within one half period, andcan have values in the range of b=0 . . . π/2

all these terms of the sum, for which the argument (2n+1)b of the cosinefunction is an odd number multiple of π/2, that is${( {{2n} + 1} )b} = {\frac{\pi}{2} \times ( {{2n} + 1} )}$are missing.

Whereas the lower order higher harmonics cause the most significanterrors of synchronous demodulation, then the values for the zero valueintervals b can be found from the following simple conditions:to remove the 3rd harmonic, 3b=π/2,

b=π/6 or 30°,to remove the 5th harmonic, 5b=π/2,

b=π/10 or 18°.

Applying of the above given conditions shows that the first coincidingharmonics in the excitation and reference signals are the 7th ones,which means that the measurement error is reduced about one order incomparison with the initial case of using regular rectangular waveforms(the amplitude error between −13 to +24 percent is reduced to −1.8 to+2.4 percent). Such a result meets the needs of most cases to be facedin practice.

A device for implementing of the above method for increasing theaccuracy of bio-impedance measurements contains additional functionalblocks, the task of which is to shorten the duration of the constantvalue sections of both the excitation and the reference pulse signals bypredetermined time intervals proportional to the signals periods,whereby these predetermined time intervals for the excitation signal andthe reference signal have different duration.

DESCRIPTION OF DRAWINGS

FIG. 1 is a simplified graphical presentation of the method formeasurement of the electrical bio-impedance together with the signalwaveforms of essential inputs.

FIG. 2A shows on period of differently shortened rectangular wave pulsesignals.

FIG. 2B gives the spectra of harmonics of the two shortened signalsshown in FIG. 2A, where the harmonics designated with “x” correspond tothe shorter pulse signal and with “o” to the wider one.

FIG. 3 is a principal block diagram of the two channel measurementdevice for measuring of mutually quadrature components of thebio-impedance according to the method presented in FIG. 1.

FIG. 4 is a circuitry of a generator of the rectangular wave signalsbased on using of a shift register and quadrature triggers.

FIG. 5 indicates the rectangular waveforms of signals generated by thegenerator depicted in FIG. 4, the arrows at the waveforms explain thesignal formation procedures.

FIG. 6 is a generator of bipolar rectangular signals, whereby the signalwaveforms are shown at the inputs and outputs.

FIG. 7 is a generator of shortened pulses, whereby the signal waveformsare shown at the inputs and outputs.

FIG. 8A is a synchronous detector based on an analogue multiplier,whereby the signal waveforms are shown at the inputs.

FIG. 8B is a synchronous detector based on using of a switching modemultiplier, whereby the signal waveforms are shown at the inputs.

DESCRIPTION OF THE INVENTION

FIG. 1 presents the method for measurement of the electrical impedanceof bio-object is described. A symmetrical bipolar pulse-form periodicalexcitation signal (electrical current or voltage) is applied to theinput 11 of the bio-object 1, a corresponding reaction of the bio-objectto the mentioned excitation signal is measured from the output 12, whichis connected to the input 201 of the synchronous detector 200. Asymmetrical bipolar pulse-form periodical signal is also applied to thereference input 202 of the synchronous detector 200, but it hasdifferent spectral content in comparison with the excitation signalapplied to the input 11 of the bio-object 1.

Multiplication of pulse-form signals causes misleading measurementerrors and uncertainty of results because of their higher harmonicscontent. Therefore, a former of shortened pulse 220 (FIG. 7) is used inthe proposed solution, the task of which is to shorten the bipolarrectangular signal so that by introducing the zero value intervalscertain spectral components of the signal are removed. For minimizationof measuring error the zero value intervals introduced into theexcitation and reference signals must be set different (FIG. 2A) so thatthe cut-offs of spectral components in these signals are placed indifferent locations on the axis of harmonics, thus providing a minimumnumber of error causing coinciding spectral components.

For example, if the zero value interval introduced into the excitationsignal has a duration equal to b=π/10 or 18°, then the excitation signaldoes not contain harmonics of the 5th, 15th, 25th, . . . order, and ifthe zero value interval introduced into the reference signal is b=π/6 or30°, then the reference signal do not contain harmonics of the 3rd, 9th,15th, . . . order, and accordingly in the spectra of these signals thefirst coinciding harmonics having non-zero value are the 7^(th)harmonics (FIG. 2B), which determine the greatest portion of theresidual measurement error.

In comparison with the prior art solutions based on using of rectangularsignals the proposed method has an error level, which is approximatelyone decimal order smaller at the output 203 of the synchronous detector200 (maximum measurement error is reduced from 24% to 2.5%), which is anerror level acceptable for most practical measurements in the respectivefield.

A device for measuring of an electrical bio-impedance in FIG. 3 has twoidentically designed but functionally differently connected quadraturemeasurement channels 2 and 2′, and a generator of quadrature drivingsignals 3, which includes of two formers of the bipolar rectangularsignal 320 and 320′, the corresponding inputs 321 and 321′ of which areconnected to the quadrature outputs 331 and 335 of the generator ofquadrature signals 300, respectively. Output 332 of the former of thebipolar rectangular signal 320 is connected to the input 221 of thedevice for generating shortened pulse 220, and also with the input 221″of the device for generating shortened pulse 220″.

The measurement channel 2 contains of the synchronous detector 200 andthe device for generating shortened pulse 220, the output 223 of whichis connected to the input 202 of the synchronous detector 200, and thesecond input 222 of which is connected to the second, auxiliary signaloutput 333 of the generator of quadrature signals 300. The input 201 ofthe synchronous detector 200 is connected to the output 12 of thebio-object 1, and the output 203 of the synchronous detector 200 isaccordingly also the first output of the device.

The measurement channel 2′ includes the synchronous detector 200′ andthe device for generating shortened pulse 220′, the output 223′ of whichis connected to the input 202′ of the synchronous detector 200′, and thesecond input 222′ of which is connected to the auxiliary signal output334 of the generator of quadrature signals 300. Input 201′ of thesynchronous detector 200′ is connected to the output 12 of thebio-object 1, and the output 203′ of the synchronous detector 200′ isaccordingly also the second output of the device.

The second input 222′ of the device for generating shortened pulse 220″and applying the excitation signal to the bio-object 1 is connected tothe assisting auxiliary signal output 332 of the generator of quadraturesignals 300, and the output 223″ is connected to the input 11 of thebio-object 1.

The generator 300 of quadrature signals (FIG. 4) includes a reversibleshift register 301 having a predetermined number of stages, andquadrature triggers 302 and 303, the task of which is to formrectangular, mutually quadrature signals 331 and 335 having thefrequency of the fundamental, and the assisting auxiliary signals 333and 334 for shortening of the rectangular signals 331 and 335, and alsoassisting auxiliary signal 332 for shortening of the rectangular signalused for excitation of the bio-object 1. In FIG. 5 there are presentedtime diagrams of the signals explaining the functioning of the generatorof driving signals.

Former 320 of the bipolar rectangular signal (FIG. 6) includes atwo-pole switch 323, which is controlled by means of the input 321, andthe first input 324 of the switch is connected to the positive referencevoltage +V_(T), and the second input 325 of said switch is connected tothe negative reference voltage −V_(T) having equal absolute value, thetask of the former 320 is to shape the rectangular form signal receivedfrom the generator of quadrature signals 300 into the bipolarrectangular signal.

The device for generating of shortened pulse 220 (FIG. 7) includes atwo-pole switch 224 controlled through the input 222, the first input225 of the switch is connected to the ground, and the second input 226is connected to the input 221 of said device 220, and the task thedevice 220 is to shorten the pulses of the bipolar rectangular signalapplied to the input of synchronous detector 200 in accordance with theassisting auxiliary signal from the generator of quadrature signals 300.

If need be, the synchronous detector 200 can be designed either on thebasis of an analog multiplier 204 (FIG. 8A) or on the basis of switchingmultiplier (FIG. 8B) including a the three-position switch 250, anamplifier 251 having positive transfer coefficient +K, and the output253 of the latter is connected to the first input 255 of the switch 250,and an amplifier 252 having a negative transfer coefficient −K, theoutput 254 of which is connected to the third input 257 of the switch250. The second input 256 of the switch is, according to the needs,either connected or not connected to the ground, thus providing a zerovalue transfer factor for the synchronous detector 200 in accordancewith the position and duration of the zero value interval in the bipolarrectangular signal applied to the reference input 202.

The measuring device with two measurement channels (FIG. 3) functions asfollows: the bio-object is excited with the bipolar rectangular signalhaving shortened pulse, the corresponding electrical reaction of thebio-object to said signal is measured by means of two identical by theirrealization but different in their functional connections measurementchannels, whereby one of these channels measures the real part R and thesecond one measures the imaginary part X of the impedance {dot over(Z)}=R+jX of the bio-object.

Symmetrical rectangular signals of fundamental frequency (FIG. 5) anddoubled frequency=auxiliary signals for shortening the pulses of thequadrature rectangular signals and the excitation signal needed forfunctioning of the device, are generated by the generator of quadraturecontrol signals 300. From the signals obtained from the outputs of thequadrature triggers the formers of the bipolar rectangular signal 320and 320′ (FIG. 5) form the bipolar rectangular signals, into which bythe devices for generating of shortened pulse 220, 220′ and 220″ thezero value intervals, having durations determined according to theauxiliary signals, are introduced, which are needed for eliminating ofthe 3^(rd) and the 5^(th) harmonics from the spectra of signals.

The measuring channel includes a synchronous detector, which can,according to the needs, be implemented on the basis of an analogmultiplier (FIG. 8A), or on the basis of switching mode multiplier(drawing in FIG. 8B). In the both cases a bipolar rectangular signalwith shortened pulses is applied to the reference input of themultiplier, with which in case of the analog multiplier the measurablesignal is multiplied directly, and which in case of switching modemultiplier is used to control the three-positional switch. The switchingmode multiplier can be implemented using both the analogue and/ordigital techniques. Commonly the synchronous detector is followed by acircuitry containing a low pass filters and amplifiers, which are notdiscussed herein in detail, which are used for separating the desiredmeasurand from the output signal of the synchronous detector andamplifying it to a level needed for the equipment which follows thedevice.

1-9. (canceled)
 10. A method for measuring of an electrical impedance ofan object using periodic non sine wave signals, the method comprising:applying an excitation signal to the object; and measuring a response tothe excitation signal using synchronous demodulation, whereas both theexcitation signal and a reference signal driving a synchronous detectorare generated from a rectangular waves, and both signals having constantvalue sections, and wherein said excitation signal or said referencesignal is modified so that constant value sections of the modifiedsignal are shortened by a predetermined first time interval, duringwhich the modified signal has different value from the constant valuesections of that signal.
 11. The method according to claim 10, whereinsaid predetermined first time interval is selected so that the 3rdharmonic of said modified signal is suppressed.
 12. The method accordingto claim 11, wherein said predetermined first time interval equals toabout approximately π/6.
 13. The method according to claim 10, whereinthe other signal is also modified so that constant value sections ofthat signal are shortened by a predetermined second time interval duringwhich the signal has different value from the constant value sections ofthat signal.
 14. The method according to claim 13, wherein said othersignal has value of zero during said predetermined first time interval.15. The method according to claim 13, wherein said predetermined secondtime interval is selected so that the 5th harmonic of the other signalis suppressed.
 16. The method according to claim 15, wherein saidpredetermined first time interval equals to about approximately π/10.17. The method according to claim 10, wherein the first signal has avalue of zero during said predetermined first time interval.
 18. Adevice for measuring of an electrical impedance of an object,comprising: first generator for generating an excitation signal, whereinthe excitation signal is a modified rectangular wave signal, wherein theexcitation signal has constant value sections, that are shortened by afirst time interval during each half period of the excitation signal tosuppress higher harmonics of the excitation signal; second generator forgenerating a reference signal, wherein the reference signal is modifiedrectangular wave signal, wherein the reference signal has constant valuesections, that are shortened by a second time interval during each halfperiod of the reference signal to suppress higher harmonics of thereference signal; and a synchronous detector, having a first input, anda reference input, wherein the excitation signal is applied to an inputof the object, a response signal is received from an output of theobject through the first input of the synchronous detector, and thereference signal is applied to the reference input.
 19. The deviceaccording to claim 18, wherein a phase shift between the excitationsignal and the reference signal is 90°.
 20. A device for measuring of anelectrical impedance, of an object, comprising: an in-phase and aquadrature measurement channels; a generator of driving signals; acircuit of an excitation signal, the output of which is connected to aninput of the object, wherein first and second outputs of the generatorof driving signals are connected to inputs and of reference circuits ofsynchronous detectors , wherein the generator of driving signalscomprises a generator of quadrature signals and two formers of thebipolar rectangular signals; the circuit of the excitation signalcomprises a device for generating a shortened pulse, the control inputof which is connected to the output of the auxiliary signal of thegenerator of quadrature signals, the input is connected to the output ofthe former of the bipolar rectangular signal, and the output isconnected to the input of the object; the reference voltage circuit ofthe synchronous detector of the in-phase measurement channel comprises adevice for generating of shortened pulse is introduced, the controlinput of which is connected to the output of the auxiliary signal of thegenerator of quadrature signals, the input is connected to the output ofthe former of the bipolar rectangular signal, and the output isconnected to the reference input of the synchronous detector; thereference circuit of the synchronous detector of the quadraturemeasurement channel comprises a device for generating of shortenedpulse, the control input of which is connected to the output of theauxiliary signal of the generator of quadrature signals, the input isconnected to the output of the former of the bipolar rectangular signal,and the output is connected to the reference input of the synchronousdetector.
 21. The device according to claim 20, wherein the generator ofquadrature signals comprises a shift register of predetermined bitlength and the quadrature triggers.
 22. The device according to claim20, wherein the synchronous detectors are implemented on the basis of aswitching multiplier.
 23. The device according to claim 22, wherein theswitching multiplier in the synchronous detectors is implemented on thebasis of digital techniques.
 24. The device according to in claim 20,wherein the synchronous detectors are implemented on the basis of ananalog multiplier.
 25. The device according to claim 23, wherein theswitching multiplier in the synchronous detectors is implemented on thebasis of mixed signal analogue/digital techniques.